The present invention relates to the field of ophthalmology. In particular, the invention relates to the treatment of glaucoma and associated elevations of intraocular pressure and to the treatment of ocular hypertension associated with other diseases or conditions.
Although the underlying causes of glaucoma are not understood, its symptoms often include elevated intraocular pressure, which may be caused either by over-production of aqueous humor or by inadequate outflow of aqueous humor. If left untreated, or if inadequately treated, glaucoma can lead to blindness or significant loss of vision. There is therefore a continuing need for therapies which control the elevated intraocular pressure associated with glaucoma.
There are currently a number of drugs utilized in the treatment of glaucoma, including: miotics (e.g., pilocarpine, carbachol and acetylcholinesterase inhibitors); sympathomimetics (e.g., epinephrine, dipivalylepinephrine and para-amino clonidine); beta-blockers (e.g., betaxolol, levobunolol and timolol); and carbonic anhydrase inhibitors (e.g., acetazolamide, methazolamide and ethoxzolamide). Miotics and sympathomimetics are believed to lower IOP by increasing the outflow of aqueous humor, while beta-blockers and carbonic anhydrase inhibitors are believed to lower IOP by decreasing the formation of aqueous humor. All four types of drugs have potentially serious side effects. Miotics such as pilocarpine can cause blurring of vision and other, visual side effects, which may lead either to decreased patient compliance or to termination of therapy. Carbonic anhydrase inhibitors can also cause serious side effects which affect patient compliance and/or necessitate the withdrawal of treatment. Moreover, at least one beta-blocker, timolol, has increasingly become associated with serious pulmonary side effects attributable to its effect on beta-2 receptors in pulmonary tissue.
A significant number of glaucoma patients require the administration of more than one type of drug in order to achieve therapeutic control over their intraocular pressure (IOP). That is, a single drug does not provide adequate control of IOP in these patients. Treatment which includes the use of two or more of the above-cited classes of drugs requires the patient to apply the compositions to the affected eye(s) in separate, spaced dosages several times a day. Patient compliance with such complicated dosage regimens can be very poor, particularly with elderly patients. Since the majority of glaucoma patients are elderly, this is a significant problem.
In light of the foregoing circumstances, it is clear that a need exists for new, more potent anti-glaucoma compositions which avoid or reduce the above-cited side effects, while increasing patient compliance. The present invention is directed to such compositions.